Targeted Blocking Of Cell Death Prevents Fatal Condition Septic Shock

Ghent, Belgium 27 December 2011 - Researchers of VIB and UGent have discovered a new approach to preventing septic shock, an often fatal extreme inflammatory reaction of the body. It is the most
frequent cause of death at intensive care departments in hospitals. In sepsis, acute inflammation is attended by low blood pressure and blood clots, causing the organs to stop working. Only
recently, the Brazilian football legend Socrates, died of the consequences of this condition. In a new study in the top journal Immunity, Peter Vandenabeele and colleagues of
VIB-UGent described how blocking a particular form of cell death (necroptosis) fully protects mice against this fatal inflammation.

"This research opens up new perspectives for the treatment of fatal inflammatory diseases such as sepsis," says researcher Peter Vandenabeele of VIB and UGent. "By blocking necroptosis, we have
found a possibly new target for a therapy."

Sepsis and SIRS:

The Ghent scientists studied the Systemic Inflammatory Response Syndrome (SIRS). This is a severe inflammatory reaction affecting the entire body. It may be caused by an infection, such as
sepsis, or by physical injury such as severe burns or a serious road accident.

Role of TNF in SIRS:

The cytokine tumor necrosis factor (TNF) plays a crucial role in the occurrence of SIRS. The presence of TNF may trigger the cells to cause inflammation and programmed cell death. Inflammation is
a necessary response in the body generated, among other things, to prevent or restore damage when injury and infections have been sustained. Programmed cell death can occur in two ways: via
apoptosis or via necroptosis. The difference between the two forms of cell death lies among other things in communication with our immune system. Necroptosis usually provokes a strong reaction by
the immune system whereas apoptosis proceeds unnoticed.

RIPK: potential therapeutic target for treatment of SIRS and sepsis:

Peter Vandenabeele and his colleagues Linde Duprez, Nozomi Takahashi and Anje Cauwels have discovered that in mice eliminating apoptosis did not have any impact on lethal SIRS whereas eliminating
nepcroptosis afforded full protection against the condition. The scientists managed to block nepcroptosis by eliminating RIPK (Receptor-interacting serine/threonine-protein kinase) molecules. The
experiments showed that RIPK plays a crucial role in SIRS and sepsis. The molecule appears to constitute a potential therapeutic target for the treatment of SIRS and sepsis. Further research
should clarify the potential applications of this discovery.